Is Gut Science Biased?

In 2007, the National Institutes of Health began the Human Microbiome Project, an effort to energize the fledgling field of microbiome research; the first step would be cataloging some of the millionsbillions trillions of microbes that inhabit the human body.

Although we’ve long known that microbes live in our guts, skin, armpits and various other locations, it wasn’t until the last decade or so that researchers have started to understand the vastness and diversity of these microbial communities (largely because they had shiny new tools to study them). The NIH had a grand plan: It would build a reference, “healthy” microbiome, one that researchers could use as a baseline for their future work. They found 300 volunteers from Houston and St. Louis, had doctors confirm that the volunteers were free of disease and then pulled microbes from various locations on their bodies.

What they eventually found “in this now famous or infamous” phase of the project, as project coordinator Lita Proctor calls it, was that the types and quantities of microbes in each participant were very different. “There was no signature or characteristic microbiome,” Proctor said. But when the researchers zoomed out they saw patterns among the microbial communities as a whole — patterns that have gone on to suggest potential links between the microbiome and inflammatory bowel syndrome, diabetes, preterm birth and mental health concerns.

The name of the Human Microbiome Project is a little misleading: These “humans” are just a fraction of the people on the planet.

This is a problem, and not just for the Human Microbiome Project. The makeup of the microbiome1 is influenced by just about everything around us and everything we put inside us. So it matters who the us is. We understand very little about how these large and complex microbial communities (for scale: the mass of microbes in our gut weighs 3 to 5 pounds, Proctor said) interact with our bodies. The vast majority of data on microbiomes across science is still mostly coming from people in the U.S., Canada and Europe, and having too narrow a sample of the population means we could be looking at the proverbial trees when what we need to understand is the whole forest.

Think about lung cancer — some people are genetically predisposed to it, but more people get it by smoking. If all of our research focused on only a handful of people with that genetic predisposition, we might not realize that smoking was the real problem. Something similar goes for the gut: We may not be able to identify the effects of certain lifestyles and food choices unless we are looking at a diverse enough array of the human experience.

Microbial science isn’t the only field in which Westerners are overrepresented. A 2010 paper published in Nature described sample bias in psychology research, dubbing this overrepresented group “WEIRD” — Western, educated, industrial, rich and democratic. Thankfully, this bias has not gone unnoticed by the scientific establishment. “We had to start somewhere, but it’s really important to look across the whole human species,” Proctor said. And over the past few years, a handful of crusaders, mainly anthropologists, have been gathering gut microbes from non-WEIRD groups, turning some things we thought we knew on their head.

“If you compared them to people in New York, there’s going to be 10,000 differences. We don’t know what has to do with the microbiome.”

Samples from 27 members of the Hadza, a hunter-gatherer tribe that mostly lives in Tanzania, showed they had little to no Bifidobacterium, a common genus of bacteria found in guts in the U.S. and once believed by many to be crucial to a healthy gut microbiome. This provided some much-needed evidence that the idea of a “healthy” human gut microbiome is built on false pretenses. The samples showed that males and females also had distinct microbiome, a gender divide that hadn’t been seen in other groups.

That these strains exist in several traditional populations currently separated by an ocean may be a clue that the genus was once ubiquitous but has gone extinct among WEIRD people, said Christina Warinner, an assistant professor of anthropology at the University of Oklahoma who has been involved in researching the microbiome of various traditional groups.3

By sampling these other groups, scientists have been able to see that a defining characteristic of WEIRD microbiomes is a general lack of diversity. That relative homogeneity has been linked to negative health outcomes. But that sometimes leads people to inappropriately describe traditional groups as having a “healthy” microbiome compared with the “unhealthy” microbiomes of WEIRD people. It has also led some researchers, armed with this data about contemporary hunter-gatherers, to make claims about the microbiomes of WEIRD ancestors.

Many of these traditional groups don’t really suffer from heart disease, diabetes and other chronic diseases that are killing people in the West. WEIRD people do, and they also generally have a less diverse microbiome. Researchers want to understand whether lifestyle changes over centuries in WEIRD groups are responsible, but in the process sometimes mistakenly connect the microbiomes of groups with traditional lifestyles to the microbiomes of WEIRD ancestors. But, as Jonathan Eisen, a professor of evolution and ecology at the University of California, Davis, said, “These people are not ancient. They live in the modern world.” Eisen also pointed out that just about everything involving the lifestyle, culture and environment of these groups is different from WEIRD people. “If you compared them to people in New York, there’s going to be 10,000 differences. We don’t know what has to do with the microbiome.”

This temptation to equate the microbiome of people with modern, traditional lifestyles with those of pre-modern humans is apparent in a study of the Baka and Bantu in the Central African Republic4 that compared their gut microbiomes with wild non-human primates from the region. The authors theorize that finding certain types of microbes among the hunter-gatherer Baka people and non-human primates, but not among the Bantu, who are traditional pastoralists, was evidence that these microbes may have once been widespread and were lost in the transition to an agriculture-based lifestyle. It’s possible that change in diet is the cause, but it could also be related to the difference in lifestyle or environment of these two groups. It’s too soon to say.

And as Warinner (who stresses that these groups are “not relics of the past”) points out, the Baka and Bantu have a lot more in common in terms of microbiome diversity than either group does with someone from St. Louis. This challenges a popular idea that agriculture is to blame for the growing list of health problems associated with an industrialized diet (a supposition that’s part of the ideology of the paleo diet). Instead, this research could be a clue that some other byproduct of industrialization has been responsible for the loss of diversity. That “something else” could be so many things. “Our industrialized supply chain is homogenized, sanitized, transported long distances, and highly bred and modified through classical or genetic engineering,” Warinner said, naming just a few items on the very long list of potential explanations that need exploring.

Warinner even questions the use of the word industrialized. “When did these gut ecologies change? We’re saying industrialized because that’s where we see the difference, but we don’t really know when this change occurred,” she said.

The solutions to chronic diseases probably won’t lie just in the bacteria. “We can’t look at the Hadza or other groups and say that’s what the hunter-gatherer microbiota is, or that it’s healthy. It’s specific to them,” said Amanda Henry, a paleoanthropologist and research leader at the Max Planck Institute in Germany who also studies the microbiome of fossils. The entire Western lifestyle, not just the microbiome, is associated with these negative health outcomes. “We take the easy options, the cheap options, the fast options, the I-don’t-feel-like-getting-off-my-couch-and-going-to-exercise-options,” Henry said over the phone.

Even if the microbes identified in traditional groups could prevent or treat some diseases, early research in mice has shown that it may not be possible to simply repopulate the gut with extinct microbes, even with a concordant change in diet. There isn’t necessarily going to be a magic microbial bullet, no matter how many cultures’ — or generations’ — worth of microbes are packed inside.

Footnotes

Although many scientists differentiate between microbiota (the organisms) and microbiome (the collective genomes of all the organisms), these words and definitions are not used consistently in the literature. For clarity, we’re using microbiome here.

We’re not talking about whole-wheat bread here. As the authors of one study of the Hadza microbiome wrote, “It is noteworthy that most of the tubers consumed by Hadza contain high moisture and tough indigestible fibres that must be expectorated as a quid during chewing.”

Warinner said she and her colleagues spent a significant amount of time deciding how to label the groups they study. “We’ve really struggled with what term to use, what’s the most appropriate way to describe these differences. There are really big differences between people who grow their own food, people who purchase their food from a globalized industrialized supply chain, and people who forage,” Warinner said. They settled on “traditional” and “industrialized,” but because they don’t yet know which aspects of the food supply contribute to differences in the groups’ microbiomes, she noted the limitations of these terms.

These two groups are fascinating to researchers because they cohabitate during certain parts of the year, though the Bantu are pastoralists and the Baka are hunter-gatherers. The two groups also have a complex relationship that has been the object of much academic debate.

Anna Maria Barry-Jester is a senior reporter at Kaiser Health News and California Healthline, and formerly a reporter for FiveThirtyEight. @annabarryjester